One of the problems observed in studies using radiolabeled MAbs for detection of human tumors is the relatively low percent of the injected dose of monoclonal antibody (MAb) per gram of tumor. Recent studies in in vivo model systems for melanoma and hepatoma, and clinical trials involving hepatoma patients have suggested enhanced deposition of radiolabeled antibody in tumors pretreated with external irradiation. One major goal of this project is to identify parameters that optimize binding of MAbs to carcinoma cells in vivo. We have recently initiated studies to determine the effect of exposure of carcinomas to external irradiation prior to localization of tumors by MAb conjugates. These studies include evaluation of the effect of external irradiation on (a) growth of carcinoma xenografts, (b) cellular integrity and the expression of TAG-72 at the cellular level, and, (c) binding of MAb B72.3 to carcinoma xenografts. One approach to the treatment of patients with peritoneal carcinoma may be direct infusion into the peritoneal cavity of radiolabeled antibody conjugates. In comparison to intravenous MAb administration, this method may improve the percent of the injected MAb dose per gram of tumor and may lead to less radiolabeled antibody in the bone marrow and, therefore, less toxicity to the patient. The second major goal of this project is to develop an in vivo model system to study immunotherapy of human carcinoma in the peritoneal cavity. These studies will include (a) determination of the animal species eliciting a pattern of clearance of MAb from the blood most comparable to that observed in the human, (b) development of a human peritoneal carcinoma xenograft in an animal model, and (c) determination of the utilty- of intraperitoneally administered MAb conjugates for therapy of carcinoma.